Alpha-synuclein (aS) is a small presynaptic protein implicated in the pathogenesis of Parkinsons disease. It partitions between an intrinsically disordered cytosolic state and a more structured vesicle-bound state. Past structural studies of aS have been based largely on the SDS detergent-bound conditions, for which aS displays two alpha-helices in the N-terminal domain and an unstructured C-terminal tail that remains free in solution. We have investigated the structure and biophysics of aS in the presence of phospholipid vesicles that mimic the membrane composition of presynaptic vesicles. Very high affinity for phospholipids is measured by NMR, yielding an affinity Kd of 50 uM, which strongly suggests that in the cellular environment the protein will be >99.9% in the membrane bound state. Transferred NOE experiments indicate that the protein is highly helical in the membrane bound state, and that in contrast to prior experimental data, the C-terminal 40 residues also participate in direct interactions with the membrane. Four distinct binding modes with the membrane can be distinguished, whose relative populations depend on the aS:lipid molar ratio. One of these binding modes is implicated in accelerated fibril formation.